Approximately 40,000 new cases of early stage transitional cell carcinoma (TCCA) present annually in the US. Over 30,000 are superficial; 75% recur; 10-15% progress to invasion. Surveillance cystoscopies are required over the patient's lifetime (about 600,000 cystoscopies annually). Early stage flat TCCA is frequently occult, routinely requiring 6 random biopsies of physician-selected sites. The MediSpectra cystoscopic spectrophotometer (CystoProbe) will examine these sites and differentiate neoplastic from non-neoplastic urothelium, and eventually, provide objective aid for staging and grading. Its use will result in earlier identification of occult TCCA, lowering progression to invasion and might half the biopsies per cystoscopy. Annual medical care costs would be reduced by about 31 million. If fewer biopsies per cystoscopy permit more cystoscopy under topical anesthesia in an office setting, annual saving could amount to >$500 million. The major medical benefits: decreased lagtime between appearance of abnormal urine cytology and the diagnosis and treatment of recurrent TCCA with possible positive impact on disease-free survival. We will fabricate a CystoProbe, perform measurements on 30 patients with previous diagnosis of bladder TCCA, and analyze the results to determine how well the CystoProbe can differentiate malignant from non-malignant urothelium and if it can do this significantly better than the urologist's eye. PROPOSED COMMERCIAL APPLICATION: At $250 per biopsy, two fewer biopsies per examination would save more than $300 million annually. If fewer biopsies permit greater use of cystoscopy under topical anesthesia in an office setting, annual saving could amount to $1.9 billion.